Skaik Younis, Vahlsing Stefanie, Goudeva Lilia, Eiz-Vesper Britta, Battermann Anja, Blasczyk Rainer, Figueiredo Constança
Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
PLoS One. 2014 Jun 11;9(2):e98936. doi: 10.1371/journal.pone.0098936. eCollection 2014.
Integrins are a large family of heterodimeric proteins that are involved in cell adhesion, migration, and proliferation. Integrin diversity and function is regulated by alternative splicing. Membrane-bound and truncated β3-integrins were shown to be key players in cancer metastasis. However, the immunomodulatory functions of the soluble (s) β3-integrin have not been investigated yet. In this study, we described a novel form of sβ3-integrin in acute myeloid leukaemia (AML) patients. Furthermore, we assessed the role of the sβ3-integrin in the modulation of natural killer (NK)-cell activity. Levels of sβ3-integrin were analysed in plasma samples of 23 AML patients and 26 healthy donors by ELISA. The capacity of sβ3-integrin to regulate NK cell activity was investigated using proliferation, cytokine secretion, and cytotoxicity assays. Circulating sβ3-integrin was detected in the plasma of 8 AML patients. NK cells showed significantly higher proliferation rates after stimulation with sβ3-integrin and IL-2, IL-15 (73%). Significant increases in the NK cells' secreted levels of TNF-α, IFN-γ were measured in presence of sβ3-integrin. In addition, sβ3-integrin caused the upregulation of Granzyme B transcripts levels as well as FasL expression levels in NK cells. Most importantly, significantly higher K562 or AML blast target cell lysis rates were observed when NK cells were exposed to sβ3-integrin. This study reports the identification of a novel sβ3-integrin in AML patients and provides novel insights into its role in the immunomodulation of NK cell activity.
整合素是一类参与细胞黏附、迁移和增殖的异二聚体蛋白大家族。整合素的多样性和功能受可变剪接调控。膜结合型和截短型β3整合素被证明是癌症转移的关键因素。然而，可溶性（s）β3整合素的免疫调节功能尚未得到研究。在本研究中，我们描述了急性髓系白血病（AML）患者中一种新型的sβ3整合素。此外，我们评估了sβ3整合素在调节自然杀伤（NK）细胞活性中的作用。通过酶联免疫吸附测定（ELISA）分析了23例AML患者和26例健康供体血浆样本中sβ3整合素的水平。使用增殖、细胞因子分泌和细胞毒性测定研究了sβ3整合素调节NK细胞活性的能力。在8例AML患者的血浆中检测到循环sβ3整合素。用sβ3整合素和白细胞介素-2、白细胞介素-15刺激后，NK细胞显示出显著更高的增殖率（73%）。在存在sβ3整合素的情况下，测定NK细胞分泌的肿瘤坏死因子-α、干扰素-γ水平显著增加。此外，sβ3整合素导致NK细胞中颗粒酶B转录水平以及FasL表达水平上调。最重要的是，当NK细胞暴露于sβ3整合素时，观察到K562或AML原始靶细胞的裂解率显著更高。本研究报告了在AML患者中鉴定出一种新型sβ3整合素，并为其在NK细胞活性免疫调节中的作用提供了新的见解。
